Greater understanding of the cellular changes in response to biomaterial topography has allowed for biomaterials to be developed that specifically alter cellular behavior to elicit more efficient tissue regeneration (Anselme et al., 2010; Hoffman-Kim et al., 2010); Lim and Donahue, 2007). Several different modalities of biomaterials are used to examine glial or neuronal responses to micro- and nano-surface topographies. For example, astroglial cells attach more strongly to microfabricated pillars rather than to smooth substrates (Turner et al., 2000). Polymer microchannels have been shown to induce hippocampal neuron polarization more so than immobilized nerve growth factor on smooth substrates (Gomez et al., 2007). Neural cell lines cultured on polymer nanowires induced these neurons to produce more neural markers in comparison to the neural cells cultured on smooth surfaces (Bechara et al., 2010).
Aligned, electrospun fibers, another type of biomaterial topography, directed the extension of neurites and helped mature Schwann cell differentiation (Corey et al., 2007; Wang et al., 2009; Chew et al., 2008). Deciphering the mechanisms by which topography influences glial or neuronal behavior in manners supportive of regeneration will lead to better biomaterial strategies to repair the injured nervous system.
Of the topographical biomaterials stated above, aligned, electrospun fibers are most commonly used to mimic the anisotropic structural assembly of axons and glia in the uninjured peripheral nervous system (Bellamkonda, 2006) and within the white matter tracts of the uninjured spinal cord (Silver and Miller, 2004). The ability of aligned, electrospun fiber topography to direct regeneration and recreate the anisotropic structure within the peripheral nerve or spinal cord is communicated clearly within recent in vivo studies (Chew et al., 2007; Kim et al., 2008; Gelain et al., 2011; Hurtado et al., 2011; Liu et al., 2012). In experimental models of spinal cord injury specifically, electrospun fiber topography was able to encourage a subset of astrocytes to migrate into an electrospun fiber-containing conduit instead of forming an astroglial scar (Hurtado et al., 2011). These studies demonstrate that electrospun fibers have the potential to not only direct axonal regeneration, but also to direct the migration of astrocytes supportive of axonal regeneration.
While it is established that aligned, electrospun topography has the ability to direct axonal regeneration within experimental models of spinal cord injury, aligned fibers also may be utilized to develop in vitro models able to recapitulate transitions from healthy tissue to injured tissue. Studies involving topographical biomaterial constructs present cells with uniform topography, and cellular responses to such topography are compared to separate cultures where cells are cultured on flat surface controls (Hurtado et al., 2011; Koppes et al., 2014).
One injury with an anisotropic-to-isotropic transition is spinal cord injury (SCI), specifically within the white matter tracts. Following SCI, the extracellular environment is drastically altered, leading to changes in the composition and organization of the extracellular matrix. Furthermore, the distribution and alignment of astrocytes at the lesion edge becomes disorganized (Silver and Miller, 2004; Wanner et al., 2013). Immediately following injury, astrocytes migrate to the lesion edge, become hypertrophic and elongated, and create a dense cellular construct (termed the glial scar) (Silver and Miller, 2004; Wanner et al., 2013). These reactive astrocytes at the lesion edge alter the extracellular environment by up-regulating axonal extension-inhibiting chondroitin sulfate proteoglycans (CSPGs) (Silver and Miller, 2004; Liu et al., 2012). Spared and regenerating axons within the white matter tract then extend to the lesion edge, where they become dystrophic (Tom et al., 2004) and are not likely to cross into the lesion site due to the presence of axonal inhibitors (Sharma et al., 2012; Pernet and Schwab, 2012) and the lack of a bridging scaffold to direct axonal regeneration (Cheng et al., 1996).
Changes in extracellular composition and cellular function are very dynamic following SCI. While in vivo rodent models can provide information representative of spinal cord injury within humans (Cheriyan et al., 2014), the surgeries require exceptional expertise. Additionally, the studies are very time consuming.